Calcium‐dependent DNA fragmentation in human synovial cells exposed to cold shock

FEBS Letters

Perotti, Mariarosa²  Vairetti, Mariapia²  Mirabelli, Francesca²  Bellomo, Giorgo²  McConkey, David J.¹  Orrenius, Sten²  Toddei, Filippo² 

[1] Department of Toxicology, Karolinska Institutet, Box 60400, S-104 01 Stockholm, Sweden;Dipartmento di Medicina Interna e Terapia Medica, Clinica Medica I, University of Pavia, 1-27100 Pavia, Italy

关键词: Apoptosis;    Endonuclease;    Calmodulin;    Protein kinase C;    PCD;    programmed cell death;    PKC;    protein kinase C;    Compound R24571 calmidizolium;    (1-[bis(4-chlorophenyl)methyl]-3-[2-(2;    4-dichlorophenyl)-2-[(2;    4-dichlorophenyl)-methoxy]-ethyl]-1-H-imidazolium chloride;    calmidazolium;    quin-2;    2-[(2-bis(carboxymethylamino-5-methylphenoxy)methyl]-6-methoxy-8-bis(carboxymethyl)aminoquinoline;    quin-2 AM;    tetraacetoxymethylester of quin-2;    EGTA;    ethylene glycol bis(β-aminoethyl ether)-N;    N'-tetra-acetic acid;    Hepes;    4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;    TPA;    12-o-tetradecanoylphorbol-13-acetate;    H-7;    1-(5-isoquinolinylsulfonyl)-2-methylpiperazine;   

DOI  :  10.1016/0014-5793(90)80040-P

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Exposure of confluent human synovial McCoy's cells to near-freezing temperatures followed by rewarming at 37°C resulted in endonuclease activation and cell death characteristic of a suicide process known as apoptosis. Both DNA fragmentation and cell killing were dependent on a sustained increase in the cytosolic Ca²⁺ concentration. Sensitivity to cold shock-induced endonuclease activation was critically dependent on the cell cycle (proliferative) status and limited to confluent cells, whereas cells in the logarithmic growth phase were completely resistant. However, DNA fragmentation was promoted in the proliferating McCoy's cells pretreated with H-7 or sphingosine, inhibitors of protein kinase C. In addition, phorbol ester, known to activate PKC, inhibited DNA fragmentation in the confluent cells. Our findings indicate that cold shock-induced DNA fragmentation in McCoy's cells is dependent on a sustained Ca²⁺ increase, and sensitivity to the process appears to be regulated by the status of protein kinase C.

【 授权许可】

Unknown